The overall objective of this project has been to interpret the cardiovascular abnormalities of copper deficiency in terms of the mechanical properties and composition of the connective tissues and the biosynthesis of their structural proteins. It is intended to apply the knowledge of the pathogenesis of this model of disease toward an understanding of the normal biogenesis and function of connective tissues. The foundation will be laid for the application of the principles established to the exploration of acquired and heritable disorders of connective tissue in man and animals. The specific aims within the overall objective stated above will be to elucidate (1) the biosynthesis of elastin, (2) properties of the elastin monomer, (3) crosslinkage of elastin and collagen, (4) fine structural organization of aortic fibers and (5) mechanical properties of aortic components, as affected by copper. Advantage will be taken of the principles established by these studies to explore (6) the structural and mechanical defects in elastic arteries in disease that are encountered occasionally in the anatomical pathology service of the hospital. The approach will be the preparation, purification and characterization of soluble elastin and soluble collagen from the aortas of copper-deficient pigs, the isolation and identification of crosslinks in the insoluble elastin and collagen and the correlation of mechanical properties with structure of the fibrous proteins of the aortas. The biosynthesis and crosslinkage of elastin in vitro will be attempted and the enzyme responsible for lysyl amine oxidation will be isolated and characterized.